Our general objectives are to continue our studies on the mechanisms of pathologic effects produced by ethanol with particular emphasis on the interaction of ethanol and malnutrition with functions and structure of the liver. Studies will be conducted by integrated biochemical and morphologic techniques, in man and in experimental animals, both in vivo and in vitro. We will take full advantage of our development in the baboon of the first and thus far unique experimental model which reproduces all aspects of human alcoholic liver disease (fatty liver, hepatitis and cirrhosis). Amino acid measurements will be used to differentiate the effects of alcohol per se from those secondary to malnutrition. The interaction of malnutrition and alcohol with lipoprotein metabolism will be assessed, particularly the extent to which nutritionally produced impairments of hepatic lipoprotein secretion aggravates the alcohol induced liver lesions. Interaction of alcohol and malnutrition with bile acid metabolism will be evaluated, including the possibility that ethanol may enhance the toxicity of therapeutically used bile acids such as chenodeoxycholic acid. We will determine the role of nutritional factors in the metabolism of acetaldehyde and its action on other tissues. We plan to investigate the effects of congeners on mitochondrial function, particularly acetaldehyde oxidation. Our baboon model of alcoholic cirrhosis will be used to elucidate the impact on dietary factors on the alcohol induced hepatic lesions. We will also study clinically significant complications of cirrhosis such as portal hypertension. The immediate objectives of this study are to elucidate the pathogenesis of complications of alcholism in liver and to define the respective role of alcohol and malnutrition. The ultimate goal is the application of this knowledge to the successful prevention and treatment of alcohol related diseases by replacing current symptomatic therapy with rational and hopefully more effective forms of management.